rs7041

This case-control study of 288 Spanish RLS patients and 325 controls examined vitamin D metabolism genes and serum vitamin D levels. Serum 25-hydroxyvitamin D levels were significantly higher in RLS patients (21.94 ng/mL vs 18.63 ng/mL, p=0.0002), but seven SNPs in VDR and GC genes showed no association with RLS risk. However, RLS patients carrying the rs7975232CC genotype had higher frequency of response to GABAergic drugs.

This case-control association study of 815 Chinese pregnant women identified five SNPs in the GC (vitamin D-binding protein) gene significantly associated with serum 25-hydroxyvitamin D concentration: rs17467825, rs4588, rs2282679, rs2298850, and rs1155563. Mean 25(OH)D level was 15.67±7.98 ng/mL with 75% prevalence of deficiency. An XGBoost model incorporating these SNPs plus environmental factors achieved AUC 0.828 for predicting 25(OH)D deficiency risk. The study suggests maternal vitamin D deficiency may increase macrosomia risk (12 of 16 macrosomic infants had deficient mothers).

In 258 chronic hepatitis C patients treated with direct-acting antivirals, VDR FokI rs10735810 T>C SNP was significantly associated with hepatocellular carcinoma (HCC) presence (p=0.013), with all CC genotype carriers remaining HCC-free. Multivariate logistic regression identified age (OR 25.41), ribavirin administration, and IL28B rs12979860 CC genotype as HCC risk factors, while VDR FokI CC genotype was protective.

This study examined genetic variants in the vitamin D pathway using GWAS data from 3,686 women of African ancestry (1,657 cases). No significant associations were found between vitamin D pathway variants and breast cancer risk overall or by estrogen receptor status (pathway P > 0.5, SNP-level P adj > 0.2). Mendelian randomization analysis showed no association with genetically predicted 25(OH)D levels (P = 0.23). However, a nonsense variant rs41302073 in TYRP1 (pigment synthesis pathway) showed a 54% increased risk of breast cancer (OR = 1.54, 95% CI = 1.24-1.91, P adj = 0.007), warranting further investigation of non-vitamin D mechanisms.

This randomized, double-blind, placebo-controlled trial examined associations between SNPs in calcium and vitamin D-related genes and bone biomarkers in 748 young military trainees. The study found that rs7041 (DBP gene) was associated with higher 25OHD (β=4.46, p=1.97E-10) and rs2228570 (VDR gene) was associated with lower P1NP (β=-4.83, p=0.04) and osteocalcin. A composite genetic risk score combining rs7041 and rs1544410 predicted differential responses to calcium and vitamin D supplementation during intensive military training.

This study examined 89 genetic sequence variants in six vitamin D metabolism pathway genes (VDR, GC, CYP24A1, CYP27A1, CYP27B1, CYP2R1) in 522 early-stage head and neck cancer patients to assess associations with overall survival and second primary cancer risk. GC rs4588 and CYP2R1 rs10500804 were associated with lower serum vitamin D levels. CYP24A1 rs2296241 (aHR 1.23, p=0.05) was significantly associated with worse overall survival, while CYP2R1 rs1993116 (aHR 0.59, p=0.001) was protective against second primary cancer, independent of serum vitamin D levels.

A retrospective association study of 206 chronic hepatitis C patients examining whether vitamin D binding protein (GC) gene polymorphisms (rs7041, rs4588) and baseline vitamin D levels predict antiviral response. In difficult-to-treat HCV genotypes, patients with vitamin D >20 ng/mL and the GC wildtype (WT+) diplotype had significantly higher sustained viral response (SVR) rates (65.5% vs 24.0%, p=0.003), with multivariate OR=4.52 (p=0.015) for vitamin D >20 + GC WT+. IL-28B rs12979860 was confirmed as a strong independent predictor of SVR across all genotypes.

This hospital-based case-control study tested eight vitamin D metabolism-related polymorphisms (rs1155563, rs7041, rs4646536, rs927650, rs2107301, rs7975232, rs757343, and rs731236) in 305 melanoma patients and 370 healthy controls. None of the eight SNPs showed significant associations with melanoma risk or melanoma prognosis (Breslow tumor thickness). All odds ratios ranged from 0.80–1.22 with 95% confidence intervals crossing 1.0 and p-values > 0.05.

This study examined associations between common variants in GC, CYP2R1, and NADSYN1/DHCR7 genes and plasma 25-hydroxyvitamin D levels in 3,210 Chinese Hans. Six variants showed significant associations with lower vitamin D levels: GC-rs4588 (β = -0.076 per risk-allele, P = 1.3 × 10⁻²⁶), GC-rs2282679 (β = -0.072, P = 4.9 × 10⁻²⁴), GC-rs7041, GC-rs1155563, NADSYN1/DHCR7-rs3829251 (β = -0.036, P = 4.7 × 10⁻⁵), and DHCR7-rs1790349 (β = -0.036, P = 5.7 × 10⁻⁵). Conditional analyses indicated that GC-rs4588 and GC-rs2282679 drive the associations at the GC locus in Chinese populations.

This study examined whether genetic variants that predict higher 25-hydroxyvitamin D (25(OH)D) levels are associated with reduced multiple sclerosis (MS) risk in 1,655 MS cases and 6,349 controls. SNPs in GC (rs2282679) were significant predictors of 25(OH)D levels but showed no association with MS risk. The CYP2R1 rs10741657 'A' allele was associated with increased 25(OH)D and reduced MS risk among HLA-DR15 negative individuals (OR=0.89, 95% CI: 0.79-1.01) but not HLA-DR15 positive individuals. CYP27B1 rs703842 'C' allele was inversely associated with MS risk, with stronger effects in HLA-DR15 negative (OR=0.79, 95% CI: 0.69-0.90) versus positive individuals (OR=0.91, 95% CI: 0.80-1.04), suggesting vitamin D's protective effect on MS may be attenuated by the HLA-DR15 risk allele.

Population-based association study of vitamin D binding protein (DBP) gene variants rs7041 (Glu416Asp) and rs4588 (Thr420Lys) in 6,181 elderly Caucasians from the Rotterdam Study. DBP haplotype 1 was associated with increased serum 25-(OH)D3 levels (P=3×10⁻⁴) and a 47% increased fracture risk in subjects with low dietary calcium intake (HR 1.47, 95% CI 1.06-2.05). Gene-gene interaction was observed between DBP and VDR haplotypes (interaction P=0.015), with combined carriers showing 33% increased fracture risk (HR 1.32, 95% CI 1.07-1.61).